Nitric oxide in the human respiratory cycle

Timothy J. McMahon, Richard E. Moon, Ben P. Luschinger, Martha S. Carraway, Anne E. Stone, Bryant W. Stolp, Andrew J. Gow, John R. Pawloski, Paula Watke, David J. Singel, Claude A. Piantadosi, Jonathan S. Stamler

Research output: Contribution to journalArticle

368 Citations (Scopus)

Abstract

Interactions of nitric oxide (NO) with hemoglobin (Hb) could regulate the uptake and delivery of oxygen (O2) by subserving the classical physiological responses of hypoxic vasodilation and hyperoxic vasconstriction in the human respiratory cycle. Here we show that in in vitro and ex vivo systems as well as healthy adults alternately exposed to hypoxia or hyperoxia (to dilate or constrict pulmonary and systemic arteries in vivo), binding of NO to hemes (FeNO) and thiols (SNO) of Hb varies as a function of HbO2 saturation (FeO2). Moreover, we show that red blood cell (RBC)/SNO-mediated vasodilator activity is inversely proportional to FeO2 over a wide range, whereas RBC-induced vasoconstriction correlates directly with FeO2. Thus, native RBCs respond to changes in oxygen tension (pO2) with graded vasodilator and vasoconstrictor activity, which emulates the human physiological response subserving O2 uptake and delivery. The ability to monitor and manipulate blood levels of NO, in conjunction with O2 and carbon dioxide, may therefore prove useful in the diagnosis and treatment of many human conditions and in the development of new therapies. Our results also help elucidate the link between RBC dyscrasias and cardiovascular morbidity.

Original languageEnglish
Pages (from-to)711-717
Number of pages7
JournalNature Medicine
Volume8
Issue number7
DOIs
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Nitric Oxide
Blood
Erythrocytes
Vasodilator Agents
Oxygen
Hyperoxia
Hemoglobins
Vasoconstrictor Agents
Vasoconstriction
Heme
Sulfhydryl Compounds
Vasodilation
Carbon Dioxide
Pulmonary Artery
Morbidity
Cells
Therapeutics
glycosylated-nitric oxide complex hemoglobin A
Hypoxia
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

McMahon, T. J., Moon, R. E., Luschinger, B. P., Carraway, M. S., Stone, A. E., Stolp, B. W., ... Stamler, J. S. (2002). Nitric oxide in the human respiratory cycle. Nature Medicine, 8(7), 711-717. https://doi.org/10.1038/nm718

Nitric oxide in the human respiratory cycle. / McMahon, Timothy J.; Moon, Richard E.; Luschinger, Ben P.; Carraway, Martha S.; Stone, Anne E.; Stolp, Bryant W.; Gow, Andrew J.; Pawloski, John R.; Watke, Paula; Singel, David J.; Piantadosi, Claude A.; Stamler, Jonathan S.

In: Nature Medicine, Vol. 8, No. 7, 2002, p. 711-717.

Research output: Contribution to journalArticle

McMahon, TJ, Moon, RE, Luschinger, BP, Carraway, MS, Stone, AE, Stolp, BW, Gow, AJ, Pawloski, JR, Watke, P, Singel, DJ, Piantadosi, CA & Stamler, JS 2002, 'Nitric oxide in the human respiratory cycle', Nature Medicine, vol. 8, no. 7, pp. 711-717. https://doi.org/10.1038/nm718
McMahon TJ, Moon RE, Luschinger BP, Carraway MS, Stone AE, Stolp BW et al. Nitric oxide in the human respiratory cycle. Nature Medicine. 2002;8(7):711-717. https://doi.org/10.1038/nm718
McMahon, Timothy J. ; Moon, Richard E. ; Luschinger, Ben P. ; Carraway, Martha S. ; Stone, Anne E. ; Stolp, Bryant W. ; Gow, Andrew J. ; Pawloski, John R. ; Watke, Paula ; Singel, David J. ; Piantadosi, Claude A. ; Stamler, Jonathan S. / Nitric oxide in the human respiratory cycle. In: Nature Medicine. 2002 ; Vol. 8, No. 7. pp. 711-717.
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